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Updated: Apr 25, 2026

Chemical Inactivation of the E3 Ubiquitin Ligase Cereblon by Pomalidomide-based Homo-PROTACs
Published on: May 15, 2019
The evolving tale of immunomodulatory drugs and cereblon
1Department of Medicine, Roswell Park Cancer Institute, Buffalo, New York, USA.
Abstract:
The immunomodulatory drugs (IMiDs), of which thalidomide was the first in class, have had a complex therapeutic history. Although these drugs are now widely used to treat multiple myeloma, the precise molecular mechanism of action of these agents has remained elusive. The finding that IMiDs bind cereblon, with subsequent activation of E3-ubiquitin ligase activity and degradation of the key transcription factors IKZF1 and IKZF3, has provided insight into these drugs but leaves many questions unanswered.
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